南方医科大学学报杂志最新文献

Objective: To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.

Methods: KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues, 4 gastric adenocarcinoma cell lines (MKN-28, HGC-27, CRL-5822, and SNU-1) and normal human gastric mucosal GES-1 cells. In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression, cell proliferation, migration, invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay, Transwell migration and invasion assays, and Western blotting. In BALB/c-nude mice, HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.

Results: Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells. In HGC-27 cells, KHSRP knockdown significantly inhibited cell proliferation, migration and invasion, while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells. In nude mice, inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight, slower cell proliferation rate and fewer lung metastatic foci, and KHSRP-overexpressing SNU-1 cells produced the opposite results. KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3, which were obviously increased in KHSRP-overexpressing SNU-1 cells.

Conclusion: High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

Objective: To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.

Methods: Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting.

Results: The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats.

Conclusion: Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Objective: To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.

Methods: The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR, and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0. Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1. Breast cancer MCF-7 cells were transfected via liposome, miR-6838-5p mimic, miR-6838-5p inhibitor, DDR1 siRNA, DDR1-overexpresisng vector, or both miR-6838-5p mimic and DDR1-overexpressing vector, and the changes in cell proliferation were examined with CCK-8 and EdU assays; Western blotting was used to detect the expression of DDR1. The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.

Results: The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells. In MCF-7 cells, miR-6838-5p overexpression induced significant inhibition of cell proliferation. Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1 (P < 0.01). Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells, and DDR1 overexpression promoted proliferation of the cells; co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation. In the tumor-bearing nude mice, the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.

Conclusion: Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective: To analyze the causal relationship of gluteal tendinitis and primary coxarthrosis with the occurrence of iliotibial band syndrome using Mendelian randomization.

Methods: The GWAS data of gluteal tendinitis, primary coxarthrosis and iliotibial band syndrome were screened for high correlation single-nucleotide polymorphisms (SNPs). Mendelian randomization analysis was performed using random-effects inverse variance weighting (IVW), MR-Egger regression, and weighted median method to determine whether gluteal tendinitis and primary coxarthrosis were causally related with iliotibial band syndrome. Heterogeneity test, multiple validity test and sensitivity analysis, and clinical data analysis were used to verify the reliability of the results.

Results: Both gluteal tendinitis [IVW: OR(95% CI)=1.32 (1.03-1.68), P=0.026] and primary coxarthrosis [IVW: OR (95% CI)=1.40 (1.06-1.84), P=0.017] was positively correlated with iliotibial band syndrome.

Conclusion: Gluteal tendinitis and primary coxarthrosis may increase the risk of iliotibial band syndrome.

Circulating tumor cells (CTCs) are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence. CTCs contain complete pathological information, which can be extracted by isolation, enrichment, and analysis of the CTCs to guide cancer diagnosis and treatment, thereby significantly improving the monitoring efficiency and prognosis of cancer. Compared with tissue biopsy, liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience. For detection of CTCs, the cells must be captured from body fluids, followed then by their release and enrichment. This review summaries the latest research progress in responsive isolation of CTCs (e.g. with light, dielectrophoresis, acoustophoresis and magnetophoresis), chemical isolation (specific molecules and topological structure) and responsive release (e.g., light, electric, thermal, pH, enzyme responsiveness, and substrates break). Responsive isolation utilizes the differences in physical properties between CTCs and blood cells, while chemical isolation utilizes specific recognition mechanisms to capture the CTCs. These techniques result in low cell damage with a high specificity to facilitate further analysis. Currently, CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer, liver cancer, colorectal cancer, and prostate cancer.

Objective: To investigate the effect of Kaixinsan (KXS, a traditional Chinese medicine formula) for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.

Methods: Forty female BALB/c mice were randomized equally into control group, model group, and low- and high-dose KXS treatment groups, and in the latter 3 groups, mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage. Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test, and the changes in serum levels of depression-related factors were examined. RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS. The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.

Results: KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models. RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress, lipid metabolism and iron ion binding in the prefrontal cortex. Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice. In SH-SY5Y cells, both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.

Conclusion: KXS alleviates adriamycininduced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice.

Methods: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting.

Results: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues.

Conclusion: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.

Objective: To evaluate the performance of magnetic resonance imaging (MRI) multi-sequence feature imputation and fusion mutual model based on sequence deletion in differentiating high-grade glioma (HGG) from low-grade glioma (LGG).

Methods: We retrospectively collected multi-sequence MR images from 305 glioma patients, including 189 HGG patients and 116 LGG patients. The region of interest (ROI) of T1-weighted images (T1WI), T2-weighted images (T2WI), T2 fluid attenuated inversion recovery (T2_FLAIR) and post-contrast enhancement T1WI (CE_T1WI) were delineated to extract the radiomics features. A mutual-aid model of MRI multi-sequence feature imputation and fusion based on sequence deletion was used for imputation and fusion of the feature matrix with missing data. The discriminative ability of the model was evaluated using 5-fold cross-validation method and by assessing the accuracy, balanced accuracy, area under the ROC curve (AUC), specificity, and sensitivity. The proposed model was quantitatively compared with other non-holonomic multimodal classification models for discriminating HGG and LGG. Class separability experiments were performed on the latent features learned by the proposed feature imputation and fusion methods to observe the classification effect of the samples in twodimensional plane. Convergence experiments were used to verify the feasibility of the model.

Results: For differentiation of HGG from LGG with a missing rate of 10%, the proposed model achieved accuracy, balanced accuracy, AUC, specificity, and sensitivity of 0.777, 0.768, 0.826, 0.754 and 0.780, respectively. The fused latent features showed excellent performance in the class separability experiment, and the algorithm could be iterated to convergence with superior classification performance over other methods at the missing rates of 30% and 50%.

Conclusion: The proposed model has excellent performance in classification task of HGG and LGG and outperforms other non-holonomic multimodal classification models, demonstrating its potential for efficient processing of non-holonomic multimodal data.

Objective: To analyze the expression of SPAG5 in gastric cancer tissues and its regulatory roles in gastric cancer cell growth.

Methods: TCGA analysis, immunohistochemistry, and immunofluorescence staining were used to analyze the expression patterns of SPAG5 and MKi67 in gastric cancer and adjacent tissues. In gastric cancer AGS and MGC803 cells, the effects of lentivirus-mediated SPAG5 knockdown on cell growth and apoptosis were evaluated using Celigo, MTT, clone formation assays and flow cytometry.

Results: Proteinatlas and TCGA database analysis suggested that SPAG5 was highly expressed in gastric cancer, and Kaplan-Meier analysis and GEPIA analysis showed high expressions of SPAG 5 in lung adenocarcinoma, breast cancer, hepatocellular carcinoma, pancreatic carcinoma, cervical cancer and bladder carcinoma. Immunohistochemistry revealed that SPAG5 was highly expressed in gastric cancer tissues (P < 0.001), and immunofluorescence colocalization analysis demonstrated a significant correlation between SPAG5 and MKI67 (R=0.393, P < 0.001). RT-qPCR and Western blotting showed that SPAG5 was highly expressed in MKN74, BGC823, MGC803, SGC7901 and AGS cells. In AGS and MGC803 cells, SPAG5 knockdown significantly inhibited proliferation and promoted apoptosis.

Conclusions: The expressions of SPAG5 and MKi67 are correlated in gastric cancer tissues, and SPAG5 knockdown inhibits the proliferation of gastric cancer cells. SPAG5 is associated with the prognosis of gastric cancer patients and may serve as a promising biomarker for gastric cancer.

Objective: To investigate the effects of kuwanon G (KG) on proliferation, apoptosis, migration and invasion of gastric cancer cells and the molecular mechanisms.

Methods: The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay, by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67. The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit, Western blotting and TUNEL staining. The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase (MMP). The role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in KG-mediated regulation of gastric cancer cell proliferation, migration, and invasion was verified by Western blotting and rescue assay.

Results: KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner (P < 0.05). KG treatment also increased apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, down-regulated Bcl-2, lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells (P < 0.05). Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway, and IGF-1, an activator of the PI3K/AKT/mTOR pathway, reversed the effects of KG on proliferation, migration and invasion of gastric cancer cells (P < 0.05).

Conclusion: KG inhibits proliferation, migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.